The purpose of this research is to critically examine selected immunoregulatory parameters which are believed to be most relevant to the ultimate fate of the human patient with lung cancer. The current project describes the use of athymic (nude) mice as individualized in vivo assay systems for evaluating the effects of human tumor-bearing host cells and/or humoral factors on tumor growth. The growth of individual tumors is a desirable step in evaluating not only a particular individual's immune potential, but also in determining the efficacy of various forms of therapy in a particular host-tumor system. For patients whose tumors are not resectable or are not amenable to growth either in vitro or in vivo, established lung tumor cell lines, especially oat cell carcinoma SHP-77, are being used as model systems to evaluate patient immune factors. Blood samples are being studied from patients with different lung cancers, especially small cell carcinoma. Major emphasis is placed on two additional parameters of patient immune competence, i.e., flow cytometric analysis of patient peripheral blood lymphocytes (PBL), using fluorescence-labeled monoclonal antibodies for identifying T-cell subsets in conjunction with in vitro 51Cr-\or 111In-release cytotoxicity assays for natural killer (NK) cells. These studies will help definethe immunological status of cancer patients and provide a framework for developing methods for immunological engineering; whereby immunization of individual cancer patients with either specific or nonspecific forms of immunotherapy, in combination with other treatment modalities, will achieve the greatest benefit for the patient. Thus far, immunoreactivity in 18 patients with small cell lung cancer has been evaluated in vitro, and 7 in vivo in nude mice. 51Cr-\or 111In-release cytotoxicity assays and flow cytometer assays with monoclonal antibodies to identify T-cell subsets of patient PBL show marked heterogeneity among patients. Relative numbers of T-cell subsets do not appear to relate to functional activity of patient PBL either in vitro or in vivo in nude mice. Longitudinal studies of two patients with oat cell carcinoma indicate that patient PBL do not cause graft versus host disease in nude mice, but can enhance growth of oat cell carcinoma tissue culture line SHP-77 in BALB/c nu nu hosts. Data therefore suggest that multiple parameters are needed to monitor disease progression to optimize treatment for each patient.